Tau (Neurofibrillary tangle protein, Paired helical filament-tau, PHF-tau)

Tau is a microtubule-associated protein found predominantly in neuronal axons of the vertebrate brain. Human tau exists as six different isoforms that result from alternative splicing of the single transcript derived from a gene located on chromosome 17. The molecular weight of the tau isoforms ranges from 48 kDa to 68 kDa. Tau protein is highly soluble and normally attached to axonal microtubules. Tau stabilizes the microtubules and makes them rigid. Tau interacts with actin in the cytoskeleton and neuronal outgrowth, anchors enzymes such as protein kinases and phosphatases, and regulates intracellular vesicle transport. Tau is phosphorylated by numerous serine/threonine kinases, including GSK-3β, PKA, PKC, CDK5, MARK, JNK, p38MAPK and casein kinase II. Tau phosphorylation regulates both normal and pathological functions of this protein.